Seeing the future of histotechnology through its history

Earlier this summer, a nine-year-old boy showed me an illustrated picture of a cell in a book titled First Human Body Encyclopedia [1]. He asked several questions such as ‘Where did the first cell come from?’ ‘Who was the first person to discover the cell?’ ‘How tiny is DNA and how can we see it?’ His questions sparked my interest in digging through the history of histology and histotechnology and made me wonder what the future holds for our profession. As histotechnologists, we all need a chance to refresh, remember our history, and appreciate the many, many years of discovery. It is not only about knowing what to do but also understanding the theory behind what we do. We also need to know how to make refinements and develop new methods when performing our jobs in histology laboratories. In an effort to better represent ourselves in the medical technology community, more than four decades ago the histotechnology professional organization, the National Society for Histotechnology (NSH) was established. We are now in a fast-changing mode of the modern world. Is there a bigger territory for NSH’s expansion? And what changes are in store for the future of histotechnology?

Centuries of legacy

Curiosity drove a nine-year-old boy to wonder who showed us the cell for the first time. Curiosity was the passion of mankind that led to explorations in the physical and biological world. Even without microscopes, people made macroscopic observations about the tissue structure of plants, animals, and the human body which can be seen in ancient Chinese and Indian literature, as well as others. However, histology as a discipline began with the invention of the light microscope in Europe. One of the first significant observations in histology came in 1665 by Robert Hooke when he used the term ‘cell’ for his findings. Shortly after Hooke’s discovery, the first use of a dye for microscopic study of biological samples was introduced by Anton Van Leeuwenhoek. Evolving from the microscopic examinations of biological specimens, the fundamental macroscopic investigations of tissues and organs by gross dissections, and the classifications done by scientists like Leonardo da Vinci, Marcello Malpighi, and Marie Francois Xavier Bichat, the term ‘histology’ was coined by Karl Meyer in 1819. The term became more widely used when supported by Sir Richard Owen in 1844 [2].

Along with the development of the histology discipline, many histological methods and techniques originated in the past couple of centuries such as fixation, paraffin infiltration and embedding, sectioning and staining with biological stains, chemistry and immunochemistry assays, nucleic acid detection, and imaging with light and electron microscopes. Each unique development of these methods and techniques could form many articles in the Journal of Histotechnology (JOH). An Internet search did not identify who termed the word ‘histotechnology.’ In Sheehan and Hrapchak’s book [3], the authors believed that combining the histology discipline with the medicine discipline led to the birth of histotechnology. From the National Society for Histotechnology, ‘histotechnology centers on the detection of tissue abnormalities and the treatment for the diseases causing the abnormalities’ and ‘histotechnology requires five basic steps including grossing and fixation, processing, embedding, sectioning and staining’ (http://www.nsh.org/about/about-histotechnology). Histological methods and techniques are not only used in clinical settings. We have seen histotechnology emerge in the veterinary discipline, pharmaceutical industry, and research laboratories. In fact, many new methods are developed on the research side and are accepted for clinical use later. Therefore, the continuous development of a sophisticated histology discipline as well as other technologies such as automation and artificial intelligence will dramatically shape the future of histotechnology.

The future of histotechnology

Predicting the future is difficult and no one really knows what will happen. However, based on the molecular, histology-aided advancement in cellular and molecular biology and the present growth of digital and artificial intelligence technology, we can imagine changes that will likely occur in the histotechnology field.

Scientists never end their quest to identify new biomarkers or to better understand the role of specific genes and their products in normal physiology or pathological changes. For example, much attention is currently being given to the cancer diagnosis and treatment field. Knowing the heterogeneity of gene expression and protein markers in different tumors at different stages is very beneficial for patient treatment. Many histotechnologists have been involved in this flow and I am sure more and more of them have noticed that their list of testing is getting longer and longer. In some cases, they may be required to multiplex several or even dozens of proteins and nuclei acid targets on the same section. Although sophisticated techniques such as cytometry and mass spectrometry-combined immunohistochemistry, single molecular in situ hybridization, and high throughput next-generation gene sequencing are still in developing phases in research settings, some of our specialists may want to pay attention to those advancements and be ready to handle clinical specimens for patient care.

With the first Federal Drug Administration (FDA) approval of a high-definition whole slide scanner, digital pathology becomes a big move that may bring changes to histology laboratories for years to come [4]. If a diagnosis can be made based on whole slide imaging, histotechnologists will be trained not only how to prepare slides for whole slide imaging but also to play a role in imaging and analyzing the digital information. We all know a comprised tissue section or stain can lead to a missed diagnosis, but this is also true if a digitalized image is not correct.

Another exciting advancement in imaging is super-resolution microscopes. For example, stimulated- emission-depletion microscopy (STED), structured illumination microscopy (SIM), and stochastic optical reconstruction microscopy (STORM) were created based on the advancement of microscope design and organic fluorescent dye synthesis. Although some histotechnologists in research institutes have combined routine histotechniques with super-resolution microscopy imaging, there are many ways they could contribute more in this area. For example, is discovering whether paraffin-embedded samples are good for super-resolution studies? Is it necessary to bring this technique to clinical settings? Whether and how light super-resolution microscopy could replace electron microscopy in some cases to make a diagnosis?

From the first enclosed tissue processor and automated stainer to the most sophisticated robotic and well-programmed instruments seen at the annual NSH Symposium and Convention, we all are witnessing non-stop innovation in the automation enabling histotechnologists to fulfill their jobs in an easier and better way. We are amazed by and appreciative of this automation, while also concerned about robotics replacing human skills. In clinical practice, examination of human specimens for patient care was standardized long ago. Although these skills will not be replaced for many years to come, we have all heard about new technologies such as Microscopy with Ultraviolet Sectioning Excitation (MUSE) and artificial intelligence-based early disease detection that may eliminate tissue processing/embedding/sectioning and staining. Histotechnologists will align themselves into the changing environment while embracing new technologies available in recent years.

Conclusion

Since the birth of histotechnology when histology met medicine a long time ago, it has never stopped changing and adapting new methods into the field. There are many challenges down the road for current and future histotechnologists, but many opportunities exist along the journey of change. Of course, clinical and human health care is critical to our community, but sometimes histotechnologists need to look back and learn in-depth about their backbone, histology. Many advancements and new technologies are emerging in the histology discipline, and sooner or later some of these newly developed concepts will force changes in many clinical laboratories. The challenges and changes are not solely imposed on histotechnologists, but it is true for JOH as well. Addressing histotechnological techniques should remain the focus of the journal. However, JOH should and will open its arms to histology research work. Remembering the beginning of our discipline and looking forward to the future of our profession, we, as a community, will continue the legacy of working together to share knowledge and educate each other to achieve better science and health care.